This research is planned to extend our previous work to the study of immunization of newborns against antigens in the gastrointestinal tract (oral immunization). This process, one of the physiologic reactions by which mammals become immunized to environmental antigens, initiates the expression of immunologic capacity in newborn infants. The effect of placentally transferred antibody on the oral immune response of newborns will be evaluated since antibody passively administered to adult rabbits can be recovered from the contents of the gastrointestinal tract. Antisera from normal and milk-intolerant infants will be compared to learn if internal determinants exposed by digestion are recognized by either group. The failure of orally immunized adult rabbits to recognize internal determinants appears to be related to the variable action of pepsin. The difference between normal and intolerant infants may be that intolerant infants digest the antigen more uniformly, resulting in immunization to new determinants. In addition, the antibodies against purified milk proteins synthesized by both groups of infants will be compared to determine differences in specificity and other immunologic parameters, such as precipitating efficiency. Circulating antigen-reactive cells also will be studied in both groups. This information will be employed in defining the local immune response to mucopolysaccharides related to the blood group substance. The long-term goals of this part of the experiment are to characterize the normal immunologic responses of the newborn, identify deviations from the normal which may be associated with disease, and provide a simple quantitative assessment of the functional capacity of the antibody produced by infants. The animal studies endeavor to provide information about the site at which circulating antibody is produced during oral immunization by studying the distribution of antibody-producing cells in the various lymphoid organs. The lamina propria will be intensely investigated and the antibody and/or antigen in thoracic duct lymph characterized. The long-term goals of the animal experiments is to define the site of the production of the circulating antibodies found following oral immunization.